Oxymorphone, generally administered in the form of its hydrochloride salt, is a potent semi-synthetic opiate analgesic, for the relief of moderate to severe pain, and has been approved for use since 1959. It can be administered as an injectable solution, suppository, tablet or extended release tablet. It is desirable to develop high purity forms of oxymorphone and a method for its synthesis.
Several methods for synthesising oxymorphone from compounds isolated from the opium poppy or compounds derived therefrom are known, for example, starting from morphine, thebaine, or from oxycodone. There remains the need for methods which permit the formation of oxymorphone with low contamination of alpha, beta unsaturated ketones. The present invention provides an improved oxymorphone product and a method for producing such oxymorphone.
U.S. Pat. No. 7,129,248 claims a process for producing oxycodone hydrochloride with less than 25 ppm of 14-hydroxycodeinone, by hydrogenating oxycodone having greater than 100 ppm 14-hydroxycodeinone. The synthetic route to oxycodone taught in US'248 starts from thebaine and produces 14-hydroxycodeinone as an intermediate product and 8,14-dihydroxy-7,8-dihydrocodeinone as a by-product resulting from over-oxidation of thebaine. During conversion of oxycodone free base to the hydrogen chloride salt, the by-product may undergo acid-catalysed dehydration and be converted into 14-hydroxycodeinone. Thus the final oxycodone hydrogen chloride salt contains unreacted 14-hydroxycodeinone as well as 14-hydroxycodeinone derived from the by-product 8,14-dihydroxy-7,8-dihydrocodeinone. A hydrogenation step is claimed to reduce contents of 14-hydroxycodeinone from at least 100 ppm to less than 25 ppm.